From April to August 1967, nine cases of a clinically distinct
illness characterized by fever and profuse sweating occurred in a
small nursery for newborns in St. Louis, Missouri. Two of the cases
were fatal. Early in the course of the outbreak the disease was
felt to be an intoxication, but the nature of the poison and the
mode of exposure of the patients remained obscure. Only after the
ninth case developed was it discovered that an antimildew agent,
containing a high concentration of sodium pentachlorophenate (the
sodium salt of pentachlorophenol), was being used in the hospital
laundry. All of the clinical, epidemiological, and biochemical
evidence indicated that this outbreak resulted from
pentachlorophenol poisoning. The only identified mode of exposure
was skin absorption of sodium pentachlorophenate residues on
diapers and other fabrics, resulting from the misuse of the
antimildew agent in the final laundry rinse.

The outstanding clinical feature of the illness was extreme
diaphoresis. Attendants consistently noticed that the infants'
clothing and brows were drenched with sweat. Nevertheless, the
neonates nursed avidly. As the disease progressed, fever rose as
high as 103 F, respiratory rates increased, and breathing became
labored, though auscultation of the lungs was normal and cyanosis
was absent. Other common findings included tachycardia,
hepatomegaly, and irritability followed by lethargy. Anorexia,
vomiting, and diarrhea were notably absent. Stiffness of the neck,
muscular fasciculations, and convulsions were not observed. Skin
rashes or evidences of inflammation or irritation of the skin were
not seen.

Laboratory tests frequently showed a progressive metabolic
acidosis, proteinuria, a rising blood urea nitrogen, and
"pneumonia" or "bronchiolitis" on X-ray. Bacterial and viral
cultures of blood, cerebrospinal fluid, nose, throat and stool
revealed no pathogens. Autopsy findings of the two fatal cases
showed fatty metamorphosis of the liver in both cases and fatty
vacuolar changes in the renal tubules of one case.

All except one of the seriously ill infants, a fatal case,
were transferred to other hospitals for treatment. After the first
fatal case occurred, the attending physicians suspected a toxic
cause and therefore promptly performed exchange transfusions on
each of the seriously ill infants who were subsequently transferred
for medical care. This treatment yielded dramatic results. Within
minutes to hours, the infants became more responsive and had less
respiratory distress. Fever and sweating disappeared, as did
metabolic acidosis. Renal function returned to normal during the
next few days. Except for the two fatal cases, recovery was
apparently complete.

The first four cases developed between April 17 and 19 among
a group of 25 infants who were in the nursery during this interval.
The first infant to become ill died. The institution was closed on
April 24 and thoroughly cleaned and disinfected before re-opening
on May 3. A second cluster of four cases occurred between May 10
and 15. One of these also was fatal. The average age of these eight
cases, at onset of illness, was 8.9 days. Several additional
suspect cases with fever and sweating were detected among 13
infants who had been discharged from the hospital in apparent
health between April 17 and May 15.

From the time of the first recognition of the outbreak, an
intensive and persistent search was made for toxic substances in
the environment of the infants. A solid-stick evaporating
deodorizer had been used without change in practice for 4 years. A
commercial exterminator had sprayed regularly with a carbamate
insecticide monthly for 2 years within the hospital, but never in
the nursery. The management of drugs and the preparation of babies'
formulas revealed no deviations that were likely to permit the
introduction of a toxic substance to this many babies.

For the preceding 10 months, a commercially available
disinfectant containing a mixture of synthetic phenolic derivatives
had been repeatedly applied to surfaces that came in contact with
infants' skin.

One-dimensional thin-layer chromatography of serum specimens
obtained from the first eight cases was performed. These tests
revealed the presence of a phenolic substance in all test
specimens, which was similar to a phenolic ingredient of the
disinfectant. This substance was thought to be the toxic chemical
causing the disease.

The nursery was closed and recleaned. Use of the suspect
disinfectant was abandoned, and all equipment that had been treated
with it was discarded or rendered free of phenolic residues by
extensive cleaning with alcohol. New linens and diapers were
purchased and the nursery reopened July 11.

On August 29, an 8-day-old infant had the acute onset of an
illness identical to the previous eight infants. The infant
received an exchange transfusion and promptly recovered. A
follow-up survey of infants discharged from the hospital in July
and August revealed six additional infants who had the
characteristic excessive sweating in a milder form of the same
syndrome.

The formerly suspect disinfectant was no longer in use.
Reinvestigation of laundry procedures disclosed a previously
overlooked source of phenols. An antimildew agent, containing 22.9
percent sodium pentachlorophenate and 4.0 percent
trichlorocarbanilide, was being used in the terminal rinse of all
nursery linens and diapers, despite a warning on the label that the
compound "must not be used" in laundering diapers.

This product had been in use in the laundry since March 1966.
The recommended quantity was one ounce of powder per laundering
cycle, but it was ascertained that the laundry was actually using
3 to 4 ounces.

Thin-layer chromatography of the serum and urine of the new
case revealed an abnormal substance with characteristics that were
identical to those detected in the previous infants' sera. Further
studies in two different laboratories with improved methods of
analysis have shown that the chemical in the urine and serum of the
new case was pentachlorophenol, and was clearly not one of the
phenolic ingredients in the previously suspected disinfectant.
Additionally, pentachlorophenol was identified in freshly laundered
diapers obtained from the nursery. The quantity of
pentachloro-phenol varied from 1.5 to 5.7 mg. per diaper.
Pentachlorophenol, when fed to rats, was found to be highly toxic
and was isolated from urine of surviving rats in concentrations
comparable to that found in the sick child. Unfortunately, no
samples from the earlier cases remained for these more
sophisticated analyses.

Actions have been instituted to prevent further illnesses that
might be caused by the misuse of this product, or two other sodium
pentachlorophenate-containing products that are recommended for
similar purposes. The manufacturer has been directed to trace all
sales and shipments of these products during the past 18 months,
and to remove such products from all hospitals and any
establishment that is involved in general laundry work. The company
has voluntarily ceased sale of these three products.

(Reported by J. Earl Smith, M.D., Health Commissioner, Division of
Health, Department of Health and Hospitals, City of St. Louis,
Missouri; L.E. Loveless, Ph.D., Chemist, Clinical Laboratories, St.
Louis, Missouri; E. A. Belden, M.D., Consultant, Communicable
Disease Control, Local Health Services Section, Division of Health,
Missouri Department of Public Health and Welfare; the Epidemiology
and Pesticides Programs of the National Communicable Disease
Center, Atlanta, Georgia; the Toxicology Section, Occupational
Health Program, National Center for Urban and Industrial Health,
Cincinnati, Ohio; and a team of EIS Officers.)

Editorial Note:

The clinical, laboratory, epidemiological, and
pathological findings, as well as the prompt response to exchange
transfusion, all indicate a toxic, rather than an infectious, cause
of this outbreak. The fever, sweating, and acidosis are consistent
with intoxication with certain phenolic derivatives, which are
known to increase the metabolic rate (1). The symptoms described
here are remarkably similar to industrial accidental poisonings
resulting from overexposure to pentachlorophenol or its sodium
salts (2,3). The exact manner in which the infants became poisoned
cannot be established, but the most reasonable explanation is
absorption through the intact skin as a result of repeated contact
with diapers, blankets, and linens containing small, but readily
absorbable, quantities of sodium pentachlorophenate. The antimildew
agent, which is labelled not for use in laundering diapers or
hospital linens, nevertheless, was in use in this hospital.
Pediatricians, hospital administrators, housekeepers, and local
health authorities should check commercial diaper services and
hospital laundries to ensure that this product is not in use.

Editorial Note -- 1996

This report, one of the first well-documented accounts of an
investigation of a noninfectious disease problem to be published in
MMWR after responsibility for the publication had been transferred
to CDC, illustrates one of the most difficult challenges facing
environmental epidemiologists -- exposure assessment. Even in acute
situations such as that described in this report, the search for a
toxic agent and the route of exposure is difficult and time
consuming. In investigations of chronic and many environmentally
related illnesses, exposures that may have occurred over an
extended period may be particularly difficult to characterize
accurately; the paucity of accurate exposure data has been termed
the "Achilles heel" of environmental epidemiology (1).

As illustrated by this investigation in St. Louis in 1967, the
use of innovative laboratory methodologies has been critical to
improving the accuracy of exposure assessments. For example, during
this investigation, epidemiologists initially relied on the
laboratory techniques of thin-layer chromotographic analysis of
patient specimens to identify a phenol as the probable etiologic
agent; more advanced laboratory methods were used to confirm the
causative role of this agent and to further focus the
investigation. Since 1967, the close collaboration between
epidemiologists and laboratory scientists during environmental
investigations has continued to strengthen, and the development of
biomarkers of exposure, disease, and susceptibility has been
critical in assisting public health scientists in exposure
assessment (2). Environmental epidemiologists in state and federal
health agencies are addressing the difficulties of accurately
classifying exposure in other innovative ways. For example,
computer mapping techniques, such as Geographic Information
Systems, have enabled investigators to more accurately use
environmental sampling data to represent individual exposure.
Finally, although the investigation in St. Louis was highly
focused, the approach to this outbreak underscored the public
health benefits of basic "shoe leather epidemiology" for solving
problems regardless of their etiology.

Original report publshed with new editorial note in MMWR
1996;45:545-9 (June 28, 1996).

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